In this proposal, we will investigate a potential new way of bone healing. It is widely known that implant materials have been used for many years to support tissue repair or regeneration. It is now thought that such implants may also induce natural bone healing responses by living tissues and cells. Specifically, bioactive glasses have shown this ability to induce osteoblast response for bone healing by releasing bioactive glass ions. The purpose of this proposed work is to explore this novel idea that bioactive glass ions play an active role in bone healing and bone regeneration. To investigate the influence of these ions on bone healing, we will examine how these glasses interact with cells from an intracellular and extracellular perspective. First, it is believed that bioactive glass ions, which are release by glasses during immersion in physiological fluid, may induce various responses by osteoblasts. Second, these bioactive glass ions (namely silicon and calcium) may combinatorially control osteoblast function such that bone regeneration is hastened or enhanced. Finally, we investigate how bioactive glasses ion release can be controlled using a programmed bioactive glass. The techniques used to determine the influence of bioactive glass ions on gene expression and extracellular activity includes gene microarrays, real time polymer chain reaction, immunoassays, and immunohistochemistry. To program bioactive glasses, chemical vapor deposition is used to build nanolayered and microlayered composite glasses that deliver target ion concentrations to cells for enhanced osteoblast function. The aims and goals of this proposed work fit into the mission of NIH, that is, improving biomaterials by improving our understanding of cell-biomaterial interactions and exploring new methods in fabricating "smart" biomaterials. The work proposed here investigates biomedical device-cell interactions for bone healing. Specifically, we wish to control and improve bone healing through controlled biomaterial degradation in physiological fluid. The proposed work is aimed at developing materials that are self-regulating for gene-related therapies. Therefore, improving our understanding of tissue-biomedical device interactions can lead to devices that improve tissue healing and ease patient suffering owed to debilitating conditions and diseased.